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Biomedical subjects

F J Gennari

Publications and source records attributed to F J Gennari.

At least 37 records · Page 2Linked to original sources
PubMed1986

Renal transplantation in diabetes mellitus. Influence of preexisting vascular disease on outcome.

We reviewed the recommendations and outcomes for all patients with diabetes mellitus and end-stage renal disease referred to the Medical Center Hospital of Vermont from 1971 through December 1983. During this period, we recommended transplantation in 53 of 73 patients evaluated. Thirty-two transplants were performed in 30 patients. Of the 30 patients, 10 had clinical vascular disease prior to transplantation, i.e., claudication, amputation, active angina, myocardial infarction, or stroke. Seven of the 10 had only claudication or amputation. These 10 patients showed a clear excess in graft failure and mortality. One- and 2-year graft survival was 37 and 13%; patient survival was 48 and 24%. By comparison, the 20 patients without evident vascular disease had 1- and 2-year graft survival rates of 83 and 75% and patient survival rates of 85% at both 1 and 2 years. The incidence of cardiovascular death in the group with vascular disease was 45% at 1 year and 63% at 2 years, as compared with none in the group without vascular disease. The high graft loss and mortality in this group after transplantation should be a major consideration when therapeutic alternatives are considered in diabetics with end-stage renal disease.

Adult↗
PubMed1986

Load dependence of proximal tubular bicarbonate reabsorption in chronic metabolic alkalosis in the rat.

Studies were undertaken in Munich-Wistar rats to determine whether maintenance of chronic metabolic alkalosis (CMA) is associated with an increase in proximal HCO3- reabsorption, or whether a reduction in glomerular filtration rate (GFR) is required to sustain the elevated plasma HCO3- concentration. Superficial single nephron glomerular filtration rate (SNGFR), and absolute proximal HCO-3 (APRHCO3) and water (APRH2O) reabsorption were measured 20 +/- 3 d after the induction of CMA in eight rats and the results compared with seven age-matched control animals. Plasma [HCO3-] was 39.1 +/- 1.8 mM in CMA rats compared with 26.0 +/- 0.4 mM in controls (P less than 0.001). In the CMA rats, SNGFR was 44.8 +/- 1.1 vs. 38.2 +/- 2.1 nl/min in controls (P less than 0.025). As a result, the single nephron filtered load of HCO3- (FLHCO3) increased from 1,147 +/- 61 pmol/min in control to 2,040 +/- 108 pmol/min in CMA (P less than 0.001). APRHCO3 increased by greater than 65%, from 970 +/- 65 pmol/min in control to 1,624 +/- 86 pmol/min in CMA (P less than 0.001). APRH2O increased from 18.4 +/- 1.6 nl/min in control to 24.0 +/- 0.8 nl/min in CMA (P less than 0.005). Tubular hypertrophy resulted in an increase in the length of the proximal convoluted tubule from 5.6 +/- 0.2 to 6.5 +/- 0.2 mm (P less than 0.005). The pattern of HCO3- reabsorption along the length of the proximal convoluted tubule in CMA was indistinguishable from that found in normal rats in which FLHCO3 was varied acutely by altering SNGFR. The increase in tubular length accounted for only 30% of the increase in APRH2O and 15% of the increase in APRHCO3. We conclude that a sustained reduction in GFR is not required for maintenance of CMA in the rat. If GFR is chronically restored to normal levels, the alkalosis is maintained by an increase in APRHCO3. The increase in reabsorption is accounted for by tubular hypertrophy, a chronic adaptive response, and a load-dependent response that is indistinguishable from that seen in normal rats when FLHCO3 is increased acutely by increasing SNGFR.

Alkalosis↗
PubMed1986

Load dependence of proximal tubular fluid and bicarbonate reabsorption in the remnant kidney of the Munich-Wistar rat.

Studies were undertaken to characterize the pattern of proximal tubular fluid (APRH2O) and bicarbonate reabsorption (APRHCO3) in the remnant kidney of euvolemic Munich-Wistar rats. The remnant kidney rats were placed on a diet containing either low or normal protein. Collections were obtained in the early, mid-, and late proximal convoluted tubule. Single nephron glomerular filtration rate (SNGFR) increased from 40.2 nl/min in controls to 58.8 nl/min in low protein remnant kidney and 78.1 nl/min in normal protein remnant kidney rats. The filtered load of bicarbonate was 1,272, 1,641, and 2,013 pmol/min, in the three groups, respectively. APRH2O and APRHCO3 increased nearly in parallel. Most of the increase in reabsorption occurred in the early proximal tubule. Tubular hypertrophy could account for at least 20-40% of the increase in reabsorption, but the majority of the increase appeared to be a delivery-dependent response similar to that observed in normal rats after an acute increase in SNGFR.

Absorption↗
PubMed1985

Load dependence of HCO3 and H2O reabsorption in the early proximal tubule of the Munich-Wistar rat.

Studies were undertaken in Munich-Wistar rats to evaluate the influence of variations in the filtered load of bicarbonate (FLHCO3) and water [single nephron glomerular filtration rate (SNGFR)] on the pattern of reabsorption along the accessible proximal tubule. SNGFR and FLHCO3 were varied by examining animals under conditions of hydropenia, plasma and extracellular volume expansion (VE), and VE plus aortic constriction. Water and HCO-3 reabsorption rates were measured at intervals along the proximal tubule, from very early segments to late segments, and these values compared with previous measurements in euvolemic rats. The earliest accessible portion of the proximal tubule reabsorbed HCO3 and water avidly; 40-55% of FLHCO3 and 18-20% of SNGFR were reabsorbed within the first millimeter. Moreover, when FLHCO3 was increased to as high as 2,400 pmol/min, HCO3 reabsorption rate in the first millimeter of the tubule increased concomitantly, reaching values as high as 1,000 pmol X mm-1 X min-1. In a similar fashion, water reabsorption in the first millimeter increased in direct relation to increases in SNGFR, reaching values as high as 13 nl X mm-1 X min-1 at SNGFR values of 70 nl/min. These results indicate that the early proximal tubule has much higher HCO3 and water reabsorptive rates and a stronger load dependence than has been found in later segments of the proximal tubule. The early proximal tubule thus appears to play a critical role in the maintenance of glomerulotubular balance.

Absorption↗
PubMed1984

Current concepts. Serum osmolality. Uses and limitations.

The serum osmolality measurement has a clearly circumscribed use in clinical medicine. Comparison of the measured osmolality with the osmolality calculated from the concentrations of the major solutes in serum gives information about large deviations in the serum water content. In addition, comparison of the measured and calculated values of osmolality provides rapid screening information about the presence of foreign low-molecular-weight solutes in the blood. Taken at face value, the test cannot be used to determine whether abnormalities in tonicity homeostasis are present. A simple and direct way to assess whether tonicity is normal is to calculate the effective osmolality from the concentrations of sodium and glucose in serum. With rare exceptions, this calculation provides the information needed to make decisions about therapy.

Blood Chemical Analysis↗
PubMed1984

Analysis of the factors influencing peritubular PCO2 in the rat.

We have developed a mathematical model to assess the relative contributions of several factors to the high CO2 partial pressures observed in rat peritubular capillaries. This model is based on a single nephron and focuses specifically on the CO2 partial pressure differences (delta PCO2) between peritubular capillaries and the afferent arteriole. The model is formulated by writing steady-state mass balances for the glomerulus, proximal tubule, and peritubular capillaries in addition to equilibrium relationships for CO2, HCO3-, blood protein buffers, and hemoglobin carbamino compounds. Principal input parameters include glomerular blood flow rate, rates of HCO3- and water reabsorption, and the rate of metabolic CO2 production. Under conditions representative of normal Munich-Wistar rats, the model predicts delta PCO2 to be 4.1 mmHg, in approximate agreement with experimental observations reported elsewhere. Metabolic CO2 production is responsible for roughly half of this predicted delta PCO2, the remainder being attributable to reabsorption processes. In examining the sensitivity of delta PCO2 to changes in physiological conditions, we consistently found it to be inversely related to glomerular blood flow rate. The influence of changes in HCO3- reabsorption on delta PCO2 is variable and highly dependent on the arterial acid-base status and the ratio of HCO3- reabsorption to water reabsorption.

Acid-Base Equilibrium↗
PubMed1984

Proximal HCO3- reabsorption and the determinants of tubular and capillary PCO2 in the rat.

Studies were carried out in Munich-Wistar rats to define the CO2 partial pressure (PCO2) profile in the surface tubules and capillaries of the kidney and to relate these measurements to proximal tubular HCO3- reabsorption, renal blood flow, and O2 consumption. In euvolemic rats, PCO2 in Bowman's space (BS) was 12.5 mmHg higher than in arterial blood, indicating CO2 addition to the arterial tree as it traverses the cortex. PCO2 further rose by 3.9 mmHg between the efferent arteriole (EA) and the peritubular capillaries (PC) (P less than 0.01) and by 4.9 mmHg between BS and the early proximal tubule (EP) (P less than 0.01). In studies with paired measurements, PCO2 in EP was 1.8 mmHg higher than in the adjacent PC (P less than 0.05). HCO3- reabsorption in EP (first 0.4-1.25 mm) was 579 pmol X min-1 X mm-1 (34.3 +/- 4.6% of the filtered load). By use of a model of facilitated diffusion of CO2 across the cell, the trans-epithelial PCO2 gradient in EP can be accounted for by the CO2 generated from HCO3- reabsorption, assuming an intracellular pH of 7.3. In the vascular compartment, roughly half the rise in PCO2 between the afferent arteriole (estimated to equal BS PCO2) and PC can be accounted for by metabolic CO2 production and half by titration of blood buffers by reabsorbed HCO3-.

Acid-Base Equilibrium↗
PubMed1983

Proximal tubular bicarbonate reabsorption and PCO2 in chronic metabolic alkalosis in the rat.

Studies were undertaken to define the pattern of proximal tubular bicarbonate reabsorption and its relation to tubular and capillary PCO2 in rats with chronic metabolic alkalosis (CMA). CMA was induced by administering furosemide to rats ingesting a low electrolyte diet supplemented with NaHCO3 and KHCO3. Proximal tubular bicarbonate reabsorption and PCO2 were measured in CMA rats either 4-7 or 11-14 d after furosemide injection, in order to study a wide range of filtered bicarbonate loads. A group of nine age-matched control animals, fed the same diet but not given furosemide, was studied for comparison. In a third group of controls, the filtered load of bicarbonate was varied over the same range as in the CMA rats by plasma infusion and aortic constriction. The CMA rats had significant alkalemia and hypokalemia (4-7 d: pH 7.58, HCO3 38.3 meq/liter, K+ 2.1 meq/liter; 11-14 d: pH 7.54, HCO3 38.1 meq/liter, K+ 2.5 meq/liter). Nonetheless, proximal bicarbonate reabsorption was not significantly different from that seen in control rats at any given load of filtered bicarbonate (from 250 to 1,300 pmol/min). In both control and CMA rats, 83-85% of the filtered bicarbonate was reabsorbed by the end of the accessible proximal tubule. These observations indicate that proximal bicarbonate reabsorption is determined primarily by the filtered load in chronic metabolic alkalosis. When single nephron glomerular filtration rate (SNGFR) is reduced by volume depletion in the early postfurosemide period, the filtered load and the rate of proximal bicarbonate reabsorption remain at or below control levels, maintaining metabolic alkalosis. In the late postfurosemide period, however, SNGFR returned to control levels in some instances. In these animals, both the filtered load and rate of proximal reabsorption were increased above the highest levels seen in control animals. The PCO2 gradient between the peritubular capillaries and arterial blood (Pc-Art) was significantly higher in CMA than in control, even though the rate of proximal bicarbonate reabsorption did not differ. Thus, proximal bicarbonate reabsorption did not appear to be the primary determinant of Pc-Art PCO2. PCO2 in the early proximal (EP) tubule was significantly higher than in either the late proximal (LP) tubule or peritubular capillaries in both control and CMA rats. The EP-LP PCO2 gradient correlated directly with proximal bicarbonate reabsorption (P less than 0.05). The small elevation in PCO2 in EP may be related to CO2 generated at this site in the process of bicarbonate reabsorption.

Absorption↗
PubMed1982

PCO2 measurements in surface proximal tubules and peritubular capillaries of the rat kidney.

PCO2 was measured in surface proximal tubules and peritubular capillaries in the rat under normal acid-base conditions and in three settings with decreased HCO3(-) reabsorption: benzolamide administration, respiratory alkalosis, and metabolic acidosis. Under normal conditions, PCO2 in the early proximal tubule (EP) was 10.5 mmHg higher than PaCO2 (P less than 0.001) and 3-4 mmHg higher than late proximal (LP) and peritubular capillary (PC) PCO2 (P less than 0.001). PCO2 in LP and PC was 7 mmHg higher than PaCO2 (P less than 0.001). Benzolamide (3 mg/kg) had no effect on the difference between PC and arterial PCO2 or between EP and PC PCO2. Increasing benzolamide to 8 mg/kg increased PCO2 in the surface structures relative to arterial PCO2 by 3-5 mmHg (P less than 0.01). Metabolic acidosis did not alter the relationships between cortical and arterial PCO2. By contrast, respiratory alkalosis decreased cortical PCO2 relative to PaCO2 by over 50%. Nonetheless, EP PCO2 was still higher than LP or PC PCO2 (P less than 0.01). Thus, reducing HCO3(-) reabsorption does not obliterate the difference between EP and LP or PC PCO2 nor does it invariably reduce PCO2 in the surface structures of the kidney relative to arterial PCO2.

Animals↗
PubMed1982

The use of magnesium-containing phosphate binders in patients with end-stage renal disease on maintenance hemodialysis.

We investigated the safety and efficacy of magnesium hydroxide as a phosphate binder in patients with end-stage renal disease on maintenance hemodialysis, 9 volunteers participated in a four-phase study during which each ingested (1) no phosphate binders, (2) magnesium hydroxide (Mg(OH)2) alone, (3) Mg(OH)2 and aluminum hydroxide (A1(OH)3) together and (4) A1(OH)3 alone. Serum magnesium (SMg) concentrations were maintained at less than 4.5 mEq/1 (2.3 mmol/l) in all subjects while they were ingesting 0.75-3 g Mg(OH)2/day and no magnesium toxicity was noted. In individuals taking a constant daily dose, SMg remained stable over 8-12 weeks. Serum phosphorus (SP) decreased from 9.0 mg/dl (2.9 mmol/l)d during the control period to 8.1 mg/dl (2.6 mmol/l) during the Mg(OH)2 period (p less than 0.05) and increased from 6.1 mg/dl (2.0 mmol/l) during the Mg(OH)2 and A1(OH)3 period to 7.0 mg/dl (2.3 mmol/l) during the Al(OH)3 period (p less than 0.05) indicating that Mg(OH)2 could significantly lower SP. However, SP was best controlled (6.1 mg/dl; 2.0 mmol/l) when Al(OH)3 and Mg(OH)2 were used together and all participants preferred the combination therapy to either of the agents alone. These results indicate that Mg(OH)2 is a potentially useful adjunct to A1(OH)3 for managing hyperphosphatemia in patients on maintenance hemodialysis. In this short-term study Mg(OH)3 for managing hyperphosphatemia in patients on maintenance hemodialysis. In this short-term study Mg(OH)2 was well tolerated and with appropriate monitoring did not cause uncontrolled hypermagnesemia. Further studies are clearly required to determine whether long-term therapy with Mg-containing agents is safe in dialysis patients.

Aluminum Hydroxide↗
PubMed1981

Dissociation of saline-induced natriuresis from urea washout in the rat.

Medullary urea washout has been postulated to play a major role in the natriuretic response to volume expansion (VE). To examine this hypothesis, renal tissue solute composition was measured in a natriuretic and nonnatriuretic model of VE. Renal tissue composition was analyzed during hydropenia, acute VE, acute VE with renal artery pressure reduced to 70 mmHg at the onset of saline loading (immediate clamping), and acute VE with renal artery pressure reduced to 70 mmHg after 45 min of saline loading (delayed clamping). Immediate clamping, a nonnatriuretic model of VE, prevented VE-induced urea washout and the increase in sodium and water content in the cortex and outer medulla. Delayed clamping, a natriuretic model of VE, produced a pattern of tissue composition very similar to immediate clamping. Tissue urea content was not significantly different in the two protocols and only minor differences in sodium and water content were noted. Thus, under these experimental conditions, VE-induced natriuresis can be dissociated from medullary urea washout, and other mechanisms must be invoked to explain the increased sodium excretion.

Animals↗
PubMed1980

Effect of benzolamide on pH in the proximal tubules and peritubular capillaries of the rat kidney.

The influence of carbonic anhydrase inhibition with benzolamide on proximal tubular and peritubular capillary pH was evaluated in the rat using a glass-membrane pH microelectrode. Control peritubular capillary pH, 7.38 +/- .02 (N=11), was significantly lower than control arterial pH, 7.44 +/- .01, p < .05. Early proximal tubular pH, 7.20 +/- .02 (N = 17), was more alkaline than late proximal tubular pH, 6.74 +/- .06 (N = 13), p < .001; pH at both sites was more acid than in the peritubular capillary, p < .001. Benzolamide treatment had no detectable effect on arterial or peritubular capillary pH, but reduced early proximal tubular pH by 0.54 pH units, to 6.66 +/- .04 (N = 13), p < .001. Late proximal pH also fell slightly to 6.57 +/- .03 (N = 14), p < .02. The results support previous observations indicating that benzolamide treatment decreases early proximal tubular pH dramatically, and provide further evidence that HCO3- reabsorption is accomplished by hydrogen ion secretion in the proximal tubule.

Animals↗